PROJECT ABSTRACT Social disconnectedness (SD; long-standing lack of social / family relationships and minimal participation in social / family activities) is a huge public health problem that is associated with a wide range of negative effects. SD has negative mental and physical health consequences, with an increased risk of early mortality comparable to that of smoking. Importantly, SD exists on a continuum. It is common among individuals with severe mental illness (SMI) such as the schizophrenia spectrum (SzS), and to a lesser extent, in bipolar disorder (BD). Social functioning impairment in these disorders has barely changed with the introduction of psychoactive medications, and it translates into the very high rates of disability associated with SzS and BD throughout the world. SD also exists in individuals in the general community. Very large gaps remain in our understanding of which factors contribute to SD, particularly the neuroscience basis for SD. Understanding the determinants of SD across a spectrum is important because it can guide recovery-based treatment interventions that target such determinants. From our previous work, we know that the determinants of social functional impairment in SzS include: 1) ability (e.g., social communication) and 2) motivation (e.g., for social approach). But we have a poor understanding of the determinants of SD across a severity spectrum that extends to the general community. In this project, we will evaluate social processing constructs from the NIMH Research Domains Criterion (RDoC) Project to identify determinants of SD in mental illness and people with SD from the community. The social processing constructs include: social approach and avoidance motivation, reception of facial communication, and understanding mental states of others. These constructs can be reliably measured at units of analysis, including: behavior (performance), physiology (electrophysiology, EEG), and circuits (functional magnetic resonance imaging, fMRI). To examine the determinants of SD across a severity spectrum, we will recruit a total 350 participants: 75 SzS, 75 BD, 75 from the community who are socially connected, and 125 from the community who report longstanding SD. A subset of 160 subjects will receive fMRI. The study aims are: 1) to evaluate the degree to which social motivation (i.e., social approach and social avoidance motivation) measured by performance, EEG, and fMRI paradigms determine SD across a severity spectrum, and 2) to evaluate the degree to which ability (i.e., social communication, perception / understanding of others) measured by performance, EEG, and fMRI paradigms determine SD across a severity spectrum. We also have two exploratory aims: 1) to determine whether there are significant interactions between the two ability constructs and social motivation in determining degree of SD, and 2) to evaluate the degree to which the RDoC social constructs are associated with subjective loneliness, controlling for SD.